Engineering the Binding Kinetics of Synthetic Polymer Nanoparticles for siRNA Delivery

Hiroyuki Koide, Tatsuya Fukuta, Anna Okishim, Saki Ariizumi, Chiaki Kiyokawa, Hiroki Tsuchida, Masahiko Nakamoto, Keiichi Yoshimatsu, Hidenori Ando, Takehisa Dewa, Tomohiro Asai, Naoto Oku, Yu Hoshino, Kenneth J. Shea

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抜粋

The affinity of a synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on-demand capture and release a target biomacromolecule. Positively charged NPs for small interfering RNA (siRNA) delivery is a case in point. The knockdown efficacy of siRNA can be strongly influenced by the binding kinetics to the NP. Here, we show that kon and koff of siRNA to NPs can be individually engineered by tuning the chemical structure and composition of the NP. N-Isopropylacrylamide-based NPs functionalized with hydrophobic and amine monomers were used. koff decreased by increasing the amount of amine groups in the NP, whereas kon did not change. Importantly, NPs showing a low koff at pH 5.5 together with a high koff at pH 7.4 showed high knockdown efficiency when NP/siRNA complexes were packaged in lipid nanoparticles. These results provide direct evidence for the premise that the efficacy of an siRNA delivery vector is linked with the strong affinity to the siRNA in the endosome and low affinity in the cytoplasm.

元の言語英語
ページ(範囲)3648-3657
ページ数10
ジャーナルBiomacromolecules
20
発行部数10
DOI
出版物ステータス出版済み - 10 14 2019

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

これを引用

Koide, H., Fukuta, T., Okishim, A., Ariizumi, S., Kiyokawa, C., Tsuchida, H., ... Shea, K. J. (2019). Engineering the Binding Kinetics of Synthetic Polymer Nanoparticles for siRNA Delivery. Biomacromolecules, 20(10), 3648-3657. https://doi.org/10.1021/acs.biomac.9b00611